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Pedagogical content knowledge (PCK) is a critical factor for education quality. This study identifies PCK of students' difficulties in learning the basics of Organic chemistry, the sources of difficulties and ways to overcome them. An inquiry was conducted with 53 teachers and interview – with 3 prominent teachers. According to the teachers, the most difficult areas are "Chemical processes" and "Experiment and research". The difficulties are due to: specific subject content (formulae, terminology, logic, representation); curriculum; school settings and students' characteristics (pre-knowledge, motivation, habits, ways of learning and action). The most effective instruction methods are: problem solving, laboratory activities, discourse, demonstration of experiments and models, problem-based learning. PCK of students' difficulties is related to other elements of the PCK (КSC, KIRS, KAs) and to subject content, pedagogy and context knowledge. Our research findings can help improve the curricula and teaching practice, and to supplement research on specific topics in science education.